1. Field of the Invention
The present invention relates to compositions and methods for diagnosing autoimmune insulin dependent diabetes mellitus (IDDM). In particular, the invention concerns the diagnosis of IDDM through the detection of a particular autoimmune immunoglobulin (Ig) in patient sera, an Ig which interferes with a pancreatic islet cell-localized glucose transporter.
2. Description of the Related Art
Insulin Dependent Diabetes Mellitus ("Type I") represents 20% of all human diabetes, and is the most serious form of the disease, with the highest morbidity and mortality. Progression of the disease is associated with a major loss of pancreatic islet .beta. cell function and cell destruction (1). This loss of pancreatic .beta. cells which is apparently quite cell-specific in its early stages since other cell populations which comprise the islets of Langerhans (o cells, .delta. cells) are unaffected (2).
The series of autoimmunologic events which give rise to IDDM, or which are otherwise involved with IDDM onset, are poorly understood. However, the disease involves a progressive reduction in the function of pancreatic islets of Langerhans .beta. cells. It has, for example, been reported that a preferential loss of insulin response to glucose occurs without a corresponding reduction of the response to certain non-glucose secretagogues, such as amino acids or isoproterenol, during development of IDDM (3).
Currently available diagnostic procedures such as blood and urine determinations diagnose IDDM only after the onset of symptomatology associated with the disease, when .beta. cell destruction is almost complete. This reduces or eliminates an ability to initiate intervention early on, when it is theoretically possible to arrest the destructive process. For this reason, a simple, rapid, and inexpensive diagnostic test capable of correctly identifying IDDM patients prior to the onset of clinical disease is needed. Currently, islet cell antibodies and insulin autoantibodies identify only about 60% of such patients.
An autoimmune etiology has been implicated in a large percentage of IDDM cases, which has led researchers to try to identify a particular target or antigen. For example, Kanatsuna et al. have reported that plasma obtained from IDDM patients soon after onset will inhibit glucose-stimulated insulin secretion by rat islets (4). Furthermore, the results from several studies employing various techniques, including immunofluorescence on tissue section, chromium.sup.51 -release, etc., have demonstrated that antibodies reactive with pancreatic islet cells are often present at the time of diagnosis of IDDM (I). Other studies have identified antibodies to a 64 kd islet membrane protein, said to be detectable prior to the onset of clinical disease, in 73% of new onset IDDM patients (6-8). However, no biological function has been ascribed this antigen, and it has not as yet been isolated or further characterized.
For the foregoing and other reasons, a need exists for a diagnostic test for IDDM that addresses one or more of the problems associated with previously available tests. For example, a test that can predict the potential for IDDM development prior to its onset, thus allowing time for intervention therapy would prove particularly useful, as would a test capable of faithfully identifying pre-onset IDDM patients with a high sensitivity. It is believed that the present invention, directed to methods for the detection of particular autoimmune antibodies, addresses at least some of these or other disadvantages associated with previous approaches to IDDM diagnosis.